Possible local interactions between noradrenergic and serotonergic systems in the dorsal raphe region of the rat were investigated by studying the effects of various drugs on depolarization (20 mmol/l K+)-induced release of [3H]5-hydroxytryptamine (5-HT) and [3H]noradrenaline (NA) in vitro using a superfusion method. Exogenous 5-HT did not influence the release of [3H]NA. However, NA (in the presence of 10 mumol/l desipramine) as well as the selective alpha 2-adrenoceptor agonists clonidine and oxymetazoline strongly inhibited [3H]5-HT release. The selective alpha 1-adrenoceptor agonists phenylephrine and methoxamine did not affect the release of either [3H]5-HT or [5H]NA. The inhibition by NA of both [3H]5-HT and [3H]NA release was not affected by the beta-adrenoceptor antagonist sotalol nor by the selective alpha 1-adrenoceptor antagonist prazosin. However, phentolamine and the selective alpha 2-adrenoceptor antagonists yohimbine and rauwolscine competitively antagonized the inhibitory effect of NA on [3H]NA release (respective pA2-values 7.5 and 8.3) and on [3H]5-HT release (respective pA2-values 7.7 and 8.2). Moreover, the release of [3H]NA and also, but to a lesser extent, that of [3H]5-HT were increased by the antagonists. It is concluded that the release of both 5-HT and NA in the dorsal raphe region may be subject to presynaptic inhibition by NA via activation of alpha 2-adrenoceptors.

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